The impact of docosahexaenoic acid status and phenylalanine control on cognitive performance in females of reproductive age with phenylketonuria 公开

Yi, Sarah (2010)

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Subtle cognitive deficits are reported in people treated early for phenylketonuria (PKU). This dissertation examines the impact of phenylalanine (Phe) and docosahexaenoic acid (DHA), one known factor and one hypothesized factor, on cognitive status in females of reproductive age with PKU.

First, we assessed the impact of a 1-week camp intervention on cognitive processing speed in females with PKU. Second, we examined the association between biomarkers of DHA status and performance on tasks of verbal ability, processing speed, and executive function in a cross-sectional study. Third, we tested the effect of supplemental DHA on processing speed and executive function in a 4.5-month parallel, randomized, placebo-controlled, double-blinded study.

In the first study, a positive effect of the camp intervention was seen on measures of cognitive processing speed and plasma Phe control at the end of the camp. Improved performance exceeded a practice effect in both measures when compared with the test-retest sample; however, a larger sample size is needed to reach statistical significance. Changes in the processing speed task requiring sustained attention corresponded with changes in plasma Phe after controlling for verbal ability. In the second study, we confirmed low levels of DHA in plasma and red blood cell (RBC) total lipid percent DHA and in the diet of participants. We found a significant relationship between RBC total lipid percent DHA and verbal ability before and after controlling for concurrent plasma Phe. Associations between DHA and measures of processing speed and executive function were not seen. In the third study, supplementation with DHA appeared to be safe and effective in increasing biomarkers of DHA; however, we failed to find an effect of DHA on measures of processing speed and executive function.

Improved DHA status in addition to adequate Phe control may benefit aspects of cognitive performance in this population. Further research is needed to clarify which domains are affected by changes in DHA status, and the length and amount of DHA that is required to see these changes. Future investigations assessing the cognitive effect of DHA should measure domains more likely to be affected including verbal ability, memory, and learning.

Table of Contents

Chapter 1. Introduction

Theoretical Underpinnings

Specific Aims & Hypotheses

Main outcome measures

Chapter 2. Background

Chapter 3. Preliminary Studies

Plasma Phe control consistently improves at the end of Metabolic Camp

Consumers of medical foods without fat do not compensate for the missing fat

Biomarkers of DHA status may not differ by type of medical food used

Biomarkers of EPA and DHA status are reduced in females with PKU

Chapter 4. Methods

Cognitive Testing

Blood collection and analysis

Diet assessment

Neurological status


Study 3 Methods

Participant assessment

Monthly data collection

Study log books

Unused supplement

Protection of Human Subjects

Inclusion of Women and Minorities

Participation of persons under the age of 21

Biostatistical Design and Analysis

Sample size calculations for Study 3

Chapter 5. Short term changes in plasma phenylalanine and cognitive processing speed in females of reproductive age with phenylketonuria attending a metabolic camp







Chapter 6. Verbal performance is associated with red blood cell docosahexaenoic acid accounting for plasma phenylalanine in females of reproductive age with phenylketonuria



Participants and Methods


Discussion and Conclusions

Chapter 7. A randomized, placebo-controlled, double-blind trial of supplemental docosahexaenoic acid on cognitive processing speed and executive function in females of reproductive age with phenylketonuria: a pilot study


1. Introduction

2. Materials and Methods

3. Results

4. Discussion

5. Conclusions

Chapter 8. Conclusions

Clinical implications

Suggestions for future research

Chapter 9. Appendix: Background

Chapter 10. Appendix: Methods

Outpatient Procedure

Inpatient Procedure

Blood processing instructions

Off Site Procedure

Group Testing (W-J III): Room Map

Group Testing (W-J III): Research Assistant Data Collection Sheet

Scoring Datasheet for W-J III Tests

Website for Study 3

Logbook for Study 3


Randomization plan

Chapter 11. Appendix: Results

Study 1

Study 2

Study 3

Chapter 12. Literature Cited

About this Dissertation

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  • English
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